Evidence reviewed on: August 27, 2026
Evidence state: Predominantly preclinical. Rat studies report molecular and model-specific findings, while the human literature is small, incompletely reported, and not a confirmatory FDA-reviewed clinical program. No FDA-approved Semax drug was identified.
This page summarizes published research and regulatory records. It does not provide medical advice or instructions for administering any substance. Research involving a compound called Semax does not establish the identity, quality, safety, or equivalence of a catalog material.
What is Semax?
Semax is a synthetic seven-amino-acid peptide with the one-letter sequence MEHFPGP, corresponding to H-Met-Glu-His-Phe-Pro-Gly-Pro-OH. The first four residues correspond to the ACTH(4-7) fragment and the final three form a Pro-Gly-Pro extension. Older papers sometimes call it an ACTH(4-10) analogue, but the actual sequence should be used when identity matters.
PubChem lists the free base as CID 9811102, molecular formula C37H51N9O10S, molecular weight 813.9 g/mol, and CAS 80714-61-0. FDA assigns UNII I5FAL2585H. FDA’s 2026 review treated Semax free base and Semax acetate as distinct bulk drug substances and noted inconsistent use of identifiers in submitted material. A name or sequence alone does not establish salt form, counterion content, purity, aggregation state, or stability.
Evidence by tier
In-vitro and ex-vivo evidence
A foundational paper reported Semax-related BDNF production in cultured rat basal-forebrain astrocytes and time-dependent, specific, reversible binding in isolated rat basal-forebrain membranes. The same paper measured BDNF protein in living rats.
These are preclinical mechanistic observations in rat-derived systems. They do not establish a validated human receptor target, cognitive effect, stroke outcome, or safety profile.
Animal evidence
Semax has been studied in rat hippocampus and in several experimentally induced focal-cerebral-ischemia models. Researchers reported changes in BDNF or trkB expression and phosphorylation, conditioned-avoidance behavior, infarct-related endpoints, and transcription or expression of neurotrophin, immune, vascular, inflammatory, and cell-death-related genes and proteins.
The studies differ in model, timing, tissue, and endpoint. A change in a rat gene, protein, infarct measure, or learned behavior is not evidence that Semax prevents or treats stroke, improves recovery, or enhances cognition in people.
Observational human evidence
No independent non-interventional human cohort establishing real-world effectiveness or safety was identified in the selected source set. Some human papers compare exposed and unexposed groups, but the intended Semax exposure places them in the interventional tier even where allocation methods are unclear.
This gap matters because small experiments cannot estimate uncommon harms, long-term outcomes, or performance across broader populations.
Interventional human evidence
An older Russian-language acute ischemic-stroke report compared 30 patients who received Semax as part of intensive therapy with 80 patients who received conventional therapy. The abstract reports faster improvement in some neurological measures, but it does not describe a modern randomized, blinded design. Selection, co-intervention, and assessment bias therefore remain plausible.
A later rehabilitation report included 110 post-stroke patients divided by rehabilitation timing and Semax exposure. It reported associations among Semax exposure, plasma BDNF, motor measures, and Barthel Index changes. The English abstract does not provide enough detail about allocation, masking, attrition, prespecified endpoints, or adverse-event capture to support a confident causal conclusion.
A study of 52 healthy participants compared Semax, Selank, and placebo with repeated resting-state functional MRI. It reported short-term functional-connectivity differences involving the amygdala and temporal cortex. An imaging endpoint does not demonstrate better memory, reduced anxiety, improved daily function, or clinical recovery.
One adjunct peptic-ulcer report described a larger healing proportion in a Semax combination group than in a comparison group, but the abstract provides limited methodological detail and itself calls for further clinical study. It is not a basis for a treatment claim.
Negative and null findings
FDA’s 2026 review found the available information insufficient to support Semax for cerebral ischemia, migraine, or trigeminal-neuralgia-related use. FDA described the pain-related reports it reviewed as small, open, uncontrolled, and inconsistent. Positive language in an individual abstract does not override the limitations of the evidence set.
The human stroke literature is small, largely available through Russian-language papers, and incompletely described in English abstracts. Key features such as allocation concealment, masking, attrition handling, prespecified analysis, and comprehensive adverse-event collection are unclear in important reports. No human pharmacokinetic evidence adequate for the proposed compounded contexts was identified in FDA’s review.
FDA also identifies potential concerns involving peptide aggregation, immunogenicity, peptide-related impurities, and limited context-specific safety information. Those are unresolved risks, not proof that every Semax material causes a particular harm.
Current U.S. status
Status checked August 27, 2026. No FDA-approved drug containing Semax free base or Semax acetate was identified. FDA’s July 2026 staff briefing states that neither is a component of an FDA-approved drug and neither has an applicable USP or National Formulary drug-substance monograph.
The section 503A nominations were withdrawn, but FDA evaluated the substances on its own initiative and proposed not adding either to the section 503A Bulks List. That proposal and an advisory-committee recommendation are not a final rule; FDA makes the final determination.
FDA’s current compounding safety-risk page lists Semax heptapeptide among withdrawn nominations associated with potential immunogenicity, aggregation, impurity, and safety-information concerns. An intervention-specific ClinicalTrials.gov search returned no exact Semax study record in this audit. The human papers above therefore do not have NCT identifiers that can be reliably assigned to them.
What the evidence does not establish
The evidence does not establish Semax as a proven intervention for stroke, migraine, pain, cognition, anxiety, ulcers, or rehabilitation. It does not establish long-term safety, a generally effective exposure context, or equivalence between a published research material and a catalog item. BDNF, transcriptomic, protein, and imaging findings should remain labeled as mechanistic or surrogate endpoints.
Frequently asked questions
What is the Semax sequence?
The free-base peptide sequence is MEHFPGP, or H-Met-Glu-His-Phe-Pro-Gly-Pro-OH. FDA treats the free base and acetate as distinct bulk drug substances, so sequence alone does not specify the complete material.
Is Semax the same as ACTH?
No. Semax contains the amino-acid sequence corresponding to ACTH(4-7), followed by Pro-Gly-Pro. It is an ACTH-fragment analogue, not the full ACTH hormone.
Do BDNF findings prove cognitive enhancement?
No. BDNF-related changes in rat tissue or human plasma are biomarkers. They do not by themselves establish better memory, attention, recovery, or clinical function.
Does Semax have human stroke evidence?
Small comparative reports exist, but their methods and reporting are insufficient for a confident efficacy conclusion. The broader evidence base is predominantly rat research, and FDA found the submitted human evidence insufficient.
Is Semax FDA approved?
No FDA-approved Semax product was identified in this audit. In July 2026, FDA staff proposed not adding Semax free base or acetate to the section 503A Bulks List. The proposal should not be described as a final rule without a later FDA action.
Primary and official sources
- NIH PubChem, “Semax,” CID 9811102: https://pubchem.ncbi.nlm.nih.gov/compound/Semax
- FDA UNII, Semax, UNII I5FAL2585H: https://precision.fda.gov/uniisearch/srs/unii/I5FAL2585H
- FDA, July 2026 Semax Pharmacy Compounding Advisory Committee briefing document: https://www.fda.gov/media/193348/download
- FDA, July 23–24, 2026 Pharmacy Compounding Advisory Committee meeting record: https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026
- FDA, current compounding safety-risk page: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
- Dolotov OV, et al. “Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain.” PMID 16635254. DOI 10.1111/j.1471-4159.2006.03658.x: https://pubmed.ncbi.nlm.nih.gov/16635254/
- Dolotov OV, et al. “Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus.” PMID 16996037. DOI 10.1016/j.brainres.2006.07.108: https://pubmed.ncbi.nlm.nih.gov/16996037/
- Dmitrieva VG, et al. “Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia.” PMID 19633950. DOI 10.1007/s10571-009-9432-0: https://pubmed.ncbi.nlm.nih.gov/19633950/
- Medvedeva EV, et al. “The peptide Semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia.” PMID 24661604. DOI 10.1186/1471-2164-15-228: https://pubmed.ncbi.nlm.nih.gov/24661604/
- Sudarkina OY, et al. “Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.” PMID 34201112. DOI 10.3390/ijms22126179: https://pubmed.ncbi.nlm.nih.gov/34201112/
- “Effectiveness of Semax in acute period of hemispheric ischemic stroke.” PMID 11517472: https://pubmed.ncbi.nlm.nih.gov/11517472/
- Gusev EI, et al. “The efficacy of Semax in the treatment of patients at different stages of ischemic stroke.” PMID 29798983. DOI 10.17116/jnevro20181183261-68: https://pubmed.ncbi.nlm.nih.gov/29798983/
- Panikratova YR, et al. “Functional Connectomic Approach to Studying Selank and Semax Effects.” PMID 32342318. DOI 10.1134/S001249662001007X: https://pubmed.ncbi.nlm.nih.gov/32342318/
- Ivanikov IO, et al. “Therapy of peptic ulcer with Semax peptide.” PMID 12459874. DOI 10.1023/a:1020621124776: https://pubmed.ncbi.nlm.nih.gov/12459874/
- ClinicalTrials.gov intervention search, Semax: https://clinicaltrials.gov/search?intr=Semax